Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, Japan.
Department of Plastic and Reconstructive Surgery, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, Japan.
EMBO Mol Med. 2018 Oct;10(10). doi: 10.15252/emmm.201809024.
Argonaute 2 bound mature microRNA (Ago2-miRNA) complexes are key regulators of the wound inflammatory response and function in the translational processing of target mRNAs. In this study, we identified four wound inflammation-related Ago2-miRNAs (, , , and ) and show that is critical for infection control. mice exhibited delayed sterile healing with prolonged neutrophil activation and interleukin-6 expression, and markedly improved repair of -infected wounds. We also showed that the expression of was regulated by CCAAT/enhancer binding protein alpha in human neutrophils after exposure to peptides. Treatment with -derived neutrophils, or antisense oligodeoxynucleotides in -infected wild-type wounds markedly improved the healing of these otherwise chronic, slow healing wounds. This study reveals how regulates the bactericidal capacity of neutrophils at wound sites and indicates that targeting might be of therapeutic benefit for infected wounds in the clinic.
Argonaute 2 结合成熟的 microRNA (Ago2-miRNA) 复合物是伤口炎症反应的关键调节剂，在靶 mRNA 的翻译处理中发挥作用。在这项研究中，我们鉴定了四个与伤口炎症相关的 Ago2-miRNAs（miR-155、miR-223、miR-146a 和 miR-125b），并表明 miR-155 对于控制感染至关重要。Ago2 缺失的小鼠表现出中性粒细胞激活和白细胞介素 6 表达延长的延迟无菌愈合，并且对 - 感染的伤口修复明显改善。我们还表明，在人类中性粒细胞暴露于 肽后，miR-155 的表达受 CCAAT/增强子结合蛋白α调节。在 - 感染的野生型伤口中用 - 衍生的中性粒细胞或 miR-155 反义寡核苷酸处理，明显改善了这些原本慢性、愈合缓慢的伤口的愈合。这项研究揭示了 miR-155 如何调节伤口部位中性粒细胞的杀菌能力，并表明针对 miR-155 可能对临床感染伤口具有治疗益处。
